Liver-derived T cell clones in autoimmune chronic active hepatitis: accessory cell function of hepatocytes expressing class II major histocompatibility complex molecules.
Thirty T cell clones were generated from T cell blasts, infiltrating the liver of autoimmune chronic active hepatitis (CAH) patients, stimulated with autologous hepatocytes expressing class II major histocompatibility complex (MHC) molecules and interleukin 2 (IL2). Sixteen clones were CD4+ and 14 were CD8+; all were CD25+ and WT31+, revealing that all cell lines expressed the alpha/beta chains of T cell receptor. Five CD4+ and 4 CD8+ T clones proliferated in response to hepatocytes expressing both class I and class II antigens. The hepatocyte recognition was MHC restricted because only class II MHC-matched hepatocytes were able to stimulate the CD4+ T clones, while only class I-matched hepatocytes stimulated CD8+ T clones, and because MoAbs to monomorphic determinants of class II antigens or to class I antigens appeared to block the response of the CD4+ and CD8+ T clones, respectively. These findings, together with the observation that autologous irradiated peripheral blood mononuclear cells (iPBMC) were unable to stimulate the clones, indicate that the response of these clones was directed to a liver membrane antigen in association with class II or class I MHC molecules on the surface of the hepatocytes. All the CD8+ T clones and 5 CD4+ T clones expressed high cytotoxic activity in a lectin-dependent cell-mediated cytotoxicity assay; 10 CD8+ and 3 CD4+ T clones also showed natural killer (NK)-like function. The cytolytic machinery was also present in those clones (both CD8 and CD4) recognizing the HLA-matched hepatocytes. All liver-derived T clones were able to produce high amounts of interferon (IFN)-gamma, as well as being capable of secreting IL2, following PHA stimulation.
Franco
A
A
Fondazione Andrea Cesalpino, Università La Sapienza, Roma, Italy.
Barnaba
V
V
Ruberti
G
G
Benvenuto
R
R
Balsano
C
C
Musca
A
A
D000917:Antibody Formation; D001327:Autoimmune Diseases / Q000473:pathology*; D002999:Clone Cells; D003602:Cytotoxicity, Immunologic; D005260:Female; D006521:Hepatitis, Chronic / Q000276:immunology*; D006801:Humans; D008099:Liver / Q000166:cytology* / Q000276:immunology; D008222:Lymphokines / Q000096:biosynthesis; D008285:Major Histocompatibility Complex / Q000502:physiology; D013601:T-Lymphocytes / Q000166:cytology*
D008222:Lymphokines